雾化吸入右美托咪定对单肺通气大鼠肺内分流及肺组织HO-1表达的影响

Effect of atomization inhalation of dexmedetomidine on Qs/Qt during one-lung ventilation and heme oxygenase-1 expression in lung tissues in rats

目的:评价雾化吸入右美托咪定对单肺通气大鼠肺内分流及肺组织血红素氧合酶-1(HO-1)的影响。方法:健康成年雄性SD大鼠48只,体质量300~350 g,按随机数字表法分为4组(n_i=12):双肺通气组(C组)、单肺通气组(O组)、静脉注射右美托咪定组(V组)和雾化吸入右美托咪定组(I组)。C组气管插管后行双肺通气1 h,潮气量10 mL/kg,通气频率60次/分,呼吸比1∶2;O组、V组及Ⅰ组气管插管后行右侧单肺通气1 h,潮气量5 mL/kg,通气频率80次/分,呼吸比1∶2。V组于术前经10 min静脉输注右美托咪定5μg/kg后,以2.5μg·kg^(-1)·h^(-1)的速率输注至实验结束,Ⅰ组采用自制装置氧气驱动术前10 min雾化吸入右美托咪定0.1μg+0.9%氯化钠溶液4 mL,氧流量为2 L/min,气管插管后持续雾化吸入右美托咪定1μg;C组及O组给予等容量0.9%氯化钠溶液。于机械通气前(T0)、机械通气结束时(T1)、机械通气后30 min(T2)时采集动脉血样,检测动脉血气,计算呼吸指数(RI)、氧合指数(OI),肺内分流(Qs/Qt)后处死大鼠,取肺组织,ELISA法检测肺组织肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)的含量,肺组织湿/干重比(W/D)和HO-1表达,观察肺组织病理学改变。结果:与C组比较,O组、V组和I组肺组织TNF-α、IL-6、IL-10含量及W/D升高,HO-1表达上调,T1、T2时RI升高,OI降低,Qs/Qt升高(P<0.05~P<0.01);与O组比较,V组和I组肺组织TNF-α、IL-6含量及W/D降低,IL-10含量升高,HO-1表达上调,RI降低,OI增高,Qs/Qt降低(P<0.01),病理学损伤减轻,V组和I组间比较各指标差异均无统计学意义(P>0.05)。结论:雾化吸入右美托咪定可减轻大鼠单肺通气所致肺损伤,其机制与其上调肺组织HO-1的表达、降低肺内分流有关。

Objective：To evaluate the effects of atomization inhalation of dexmedetomidine on heme oxygenase-1 expression in lungtissues and Qs / Qt during one-lung ventilation in rats. Methods：Forty-eight male SD rats weighed 300 - 350 g were randomly dividedinto the two-lung ventilation group（group C）,one-lung ventilation group（group O）,intravenous injection dexmedetomidine group（groupV） and atomization inhalation dexmedetomidine group（group I）（12 rats each group）. The group C was coped with two-lung ventilationfor 1 h（tidal volume of 10 mL/ kg,ventilatory frequency of 60 / min and respiration ratio of 1颐 2） after endotracheal intubation. The O,Vand I groups were treated with right lung ventilation for 1 h（tidal volume of 5 mL/ kg,ventilatory frequency of 80 / min and respirationratio of 1 2） after endotracheal intubation. The group V was injected with 5 μg / kg of dexmedetomidine at the speed of 2. 5 μg·kg- 1·h - 1from before operation to the end of operation. The group I was coped with atomization inhalation of 0. 1 μg dexmedetomidinecombined with 4 mL 0. 9% sodium chloride solution before 10 min of operation, oxygen flow for 2 L/ min, and the 1 gdexmedetomidine was continuously inhaled after endotracheal intubation. The group C and group O were coped with the same volume of0. 9% sodium chloride solution. The arterial blood gas,respiratory index（RI）,oxygenation index（OI） and Qs / Qt were detected beforemechanical ventilation（T0）,at the end of mechanical ventilation（T1） and after 30 min of mechanical ventilation（T2）. The contents ofTNF-α,IL-6 and IL-10 in lung tissue were detected using ELISA assay,the W/ D and expression of heme oxygenase-1（HO-1） wereexamined,and the pathobiology change of lung tissue was observed. Results：Compared with the group C,the contents of TNF-α,IL-6 and IL-10 in lung tissues and W/ D increased,the expression ofHO-1 upregulated, the RI at T1and T2 increased, the QIdecreased and QS / Qt increased in group O,group V and groupI（P 〈 0. 05 to P 〈 0. 01）. Compared with the group O, thecontents of TNF-α and IL-6 in lung tissues and W/ Ddecreased,the content of IL-10 increased, the expression ofHO-1 upregulated,the RI decreased,the QI increased,the QS / Qt decreased,and the pathological injury alleviated in group V and groupI（P 〈 0. 01）. The differences of all indexes between group V and group I were not statistically significant（P 〉 0. 05）. Conclusions：Theatomization inhalation of dexmedetomidine can attenuate the lung injury induced by one-lung ventilation in rats,the mechanism of whichmaybe involves in the upregulation of HO-1 expression,and decreasing of Qs / Qt.